(579f) Assessment of a Localized Bisphosphonate Therapy for Perthes Disease Using Multifunctional Gold Nanoparticles

LCPD is a juvenile form of osteonecrosis of the femoral head that presents in children aged 3 to 7 years. The etiology of Legg-Calve-Perthes disease (LCPD) has remained unknown for over a century. To date, there is no universal practice for treating LCPD largely due to the unknowns of the pathology of Perthes disease. The goal of treatment is to prevent deformity of the femoral head and incongruence of the affected hip. Studies have found osteoclastic bone resorption to be a process that is a causative factor in the formation of bone deformities arising from Perthes disease. Recently, bisphosphonates have been shown in in vitro and in vivo studies to attenuate the deformities of the femoral head when administered intravenously. Although effective, systemic delivery of bisphosphonates leads to an acute phase reaction which can be especially unfavorable for young children. We have elected to study localized delivery of bisphosphonates to the femoral head as an alternative therapy. In this study, we will exploit the optical properties of gold nanoparticles (GNPs) to track the distribution and uptake of bisphosphonate conjugated gold nanoparticles. Towards this goal, we must first establish the effects of gold nanoparticles on osteoclastogenesis and osteoclast function. Long-term goals are: 1) establish proof of concept by showing the effects of using a less potent bisphosphonate; 2) better understand the interaction of osteoclasts with non-surface modified gold nanoparticles; 3) assess the efficacy of the bisphosphonate GNP conjugate; and 4) design a more complex in vitro model that better represents the in vivo environment. Characterization of the functionalized GNP and cellular response with UV-Vis and infrared spectroscopy, dynamic light scattering (DLS), optical microscopy, and transmission electron microscopy (TEM) will be presented.